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Neurocomputing

○ Elsevier BV

Preprints posted in the last 90 days, ranked by how well they match Neurocomputing's content profile, based on 13 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

1
Slow relaxation oscillations in multi-scale adaptive next generation neural masses

Martelloni, G.; Angulo Garcia, D.; Innocenti, G.; Torcini, A.; Olmi, S.

2026-07-28 neuroscience 10.64898/2026.07.26.740760 medRxiv
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We have studied the emergence of slow relaxation oscillations in next generation neural mass models with spike frequency adaptation. Relaxation oscillations connect low firing state (Down state) to high firing state (Up state) via the slow adaptation. In the examined cases, the orbit relaxes towards the Up State via a sequence of collective damped oscillations (peaks of activity), thus revealing population bursting dynamics. The slower is the adaptation time scale the higher is the complexity (number of peaks) displayed by the relaxation oscillations. In particular, a chaos-induced spike-adding mechanism regulates the increase in the number of peaks. In analogy to what found in the Hidmarsh-Rose neuron model, two different types of chaotic behaviors have been identified: Population Spiking and Population Bursting Chaos. The increase of the adaptation strength leads to shorter (longer) Up (Down) state durations somehow mimicking the effect of charbachol in in vitro experiments, where spontaneous slow waves are observed. Indeed, the scenario depicted in [1], where an increase of the concentration of carbachol induces a transition from anesthesia-like to sleep-like dynamics is consistent with our results based on the variation of the adaptation strength. HighlightsO_LISpike Frequency Adaptation (SFA) promotes the emergence of Slow Relaxation Oscillations C_LIO_LISpike-adding mechanisms, controlled by SFA, lead to Relaxation Oscillations of increasing complexity C_LIO_LITwo types of chaotic behaviours: Population Spiking and Population Bursting Chaos C_LIO_LISFA regulates Up and Down States durations and their correlation C_LI

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CViT-ESP: Lightweight Pre-trained Vision Transformers for EEG-based Epileptic Seizure Prediction

Mohammad, U.; Parani, P.; Saeed, F.

2026-08-26 neuroscience 10.64898/2026.08.21.746341 medRxiv
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Background and Objective Epileptic seizure prediction is a critical challenge requiring the discrimination of subtle preictal physiological changes from interictal brain activity. While deep learning has shown promise in this domain, existing models often face limitations due to small EEG datasets, high computational costs for training from scratch, and a lack of patient-independent generalizability. In this paper, we present a novel framework for EEG-based seizure prediction that leverages pre-trained Vision Transformers (ViTs) through custom architectural modifications and optimized re-training strategies. Methods Our primary contributions include: [bullet]CVIT-ESP: A family of vision transformer architectures that replaces standard patch embedding layers with custom N-dimensional CNN stages to refine EEG representations. [bullet] ESPFormer: A lightweight, custom-designed transformer specifically engineered to mitigate overfitting on limited-scale EEG datasets. We identified optimal fine-tuning combinations for transformer blocks by devising a heuristic search-space reduction strategy, significantly reducing the training complexity. We validated our methods using the patient-independent MLSPred-Bench, involving 12 diverse benchmarks with varying seizure prediction horizons. Results Results demonstrate a clear progression in performance: while prior ResNet and vanilla Transformer models achieved an AUC-ROC of 69.0%, our CVIT-ESP architectures achieved the highest performance with a maximum average AUC of 76.4%. Conclusions These findings suggest that adapting pre-trained ViTs with domain-specific CNN front-ends and strategic fine-tuning offers a robust, generalizable, and resource-efficient path forward for clinical seizure prediction systems. Our code is available at: https://github.com/pcdslab/CVitEsp and https://github.com/pcdslab/ESPFormer

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EEG Pathology Detection via Clinical Concept Bottleneck Models

Radwan, M.; Yazidi, A.; Lind, P. G.

2026-10-11 neuroscience 10.64898/2026.10.04.756607 medRxiv
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Deep learning models for electroencephalography (EEG) pathology detection achieve competitive accuracy but offer limited interpretability. In this paper, we introduce concept bottleneck models (CBMs) for EEG pathology detection which use clinical EEG biomarkers computed analytically from the signal as a bottleneck to be used for prediction. Those concepts include band power, spectral ratios, alpha peak frequency and amplitude, hemispheric asymmetry and phase locking values. With the backbone based on shallow convolutional neural network (CNN), we compare a black box baseline with two variants of CBMs. The hybrid variant is a classifier receives a residual projection of the backbone features. The pure variant is a CBM where the classifier receives only the predicted concepts. Models are evaluated on abnormality detection and dementia classification followed by concept prediction quality and leakage analysis. Both CBMs approach the baseline on TUAB (82.7-82.9% vs 83.6%) and are 2-5 percentage points lower on CAUEEG (57.9-60.5% vs 62.7%). The pure CBM exhibits concept fidelity concern where the predicted concepts deviate from their ground truth values. Replacing them with their true values causes severe cost on accuracy by 26 and 22 points on TUAB and CAUEEG. The concept fidelity concern is mitigated by increasing the weight of the concept loss to match the ground truth concepts. the mitigation comes with small accuracy cost on TUAB but a relatively larger cost on CAUEEG. The code of the experiments and full logs are available at https://www.github.com/mhmdrdwn/cbm.

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Estimation of the time course of excitatory and inhibitory conductance during oscillatory periods

Delicado-Moll, R. M.; Guillamon, A.; Teruel, A. E.; Vich, C.

2026-08-11 neuroscience 10.64898/2026.08.10.743856 medRxiv
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Determining the amount of information a neuron receives per unit of time is key to understanding brain connectivity and how neural networks encode and transmit information. In particular, estimating this information flow by distinguishing between excitatory and inhibitory synaptic contributions is critical to understanding neural network function, as maintaining the excitation-inhibition (E/I) balance regulates neuronal excitability and circuit stability, whereas its disruption can lead to a plethora of brain disorders, including neurodegenerative and psychiatric conditions. However, because synaptic conductances cannot be measured directly, inverse methods are required to infer them from the membrane potential --a readily measurable quantity. Although partial solutions have been proposed, accurately estimating these conductances remains a significant challenge due to the complexity and diversity of the inputs. This is particularly true in the spiking regime, where neurons actively fire. In this work, we introduce a novel computational strategy that combines two critical metrics extracted from the time course of the membrane potential recording: the amplitude of the spike and the interspike interval. By using these quantities, the proposed method enables the accurate separation of excitatory and inhibitory contributions, yielding highly favorable results in the spiking regime. Author summaryQuantifying the continuous stream of inputs a neuron receives is key to understanding brain connectivity. Inside the brain, individual cells must maintain a tight balance between excitation and inhibition (E/I) to process information correctly, as any disruption in this equilibrium can impair its functionality. However, directly measuring the underlying excitatory and inhibitory synaptic conductances is technically challenging, and existing mathematical tools often fail when neurons enter their active firing regime. In this work, we introduce a novel computational strategy designed to extract and separate these time-varying conductances directly from the neurons spiking activity. By dynamically tracking just two accessible metrics - the amplitude of the spikes and the time intervals between them - our algorithm estimates both conductance profiles with high precision. Furthermore, we demonstrate that this procedure is highly robust against realistic experimental noise and data variability, providing an accessible framework that does not require complex hardware or an unfeasible number of repetitive experimental trials. By tracking changes in the E/I ratio of the synaptic input, this method provides an efficient approach to detecting pathological imbalances and understanding how local connectivity shapes cellular functionality.

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Decision Confidence Neuron in Echo State Network for Continual Evaluation of EEG Motor Imagery Classification Quality

Lemoine, E.; Lenfesty, B.; Mudavath, U. K. N.; Bhattacharyya, S.; Wong-Lin, K.

2026-09-04 neuroscience 10.64898/2026.08.31.748424 medRxiv
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Echo state networks (ESNs) are efficient, neuro-inspired computational frameworks well suited to time-series data. However, ESN decision confidence is typically quantified in limited ways. We propose an explicit decision-confidence readout neuron, trained from decision readout outputs, to continuously monitor confidence as decisions form. In a simulated decision task, confidence activity increased with stimulus strength, linking greater discriminability to higher confidence. We then evaluated the model on EEG-based motor imagery classification, showing that confidence activity increased with decision accuracy and discriminated correct from error decisions, particularly in higher-performing participants, reflecting human-like metacognition. Overall, this approach enables continual monitoring of decision confidence, supporting more trustworthy ESN decisions, particularly in biomedical applications.

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Predictive Feature Engineering for Stress Detection using Physiological Signals, A Comparative Study

Gonzalez Nunez, J. G.; Sabri, S.; Kebria, P.; Crook, J.; Brattain, L.

2026-07-27 bioengineering 10.64898/2026.07.24.740621 medRxiv
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This paper presents a two-stage pipeline for implicit feature engineering in time series-based physiological stress detection using electrodermal activity (EDA) signals. In the first stage, we forecast three descriptive statistics of future EDA signals over short horizons (3, 5, and 10 seconds) based on a 60-second context window. In the second stage, a lightweight linear classifier detects stress from these predicted statistics. We evaluate three forecasting architectures spanning the domain expertise spectrum: a domain-specific bidirectional long short-term memory (BiLSTM) recurrent neural network, zero-shot and fine-tuned variants of Amazon Chronos T5 time series foundation model, and the Tabular Prior-data Fitted Network (TabPFN) applied to engineered physiological features. Experiments on the publicly available Wearable Stress and Affect Detection (WESAD) dataset, comprising chest-worn multimodal physiological signals from 15 subjects under baseline and stress conditions, demonstrate that the domain-specific BiLSTM achieves the highest classification performance, with area under the receiver operating characteristic curve (AUC) values ranging from 0.913 to 0.962. TabPFN follows with AUC values of 0.853-0.869, while Chronos variants yield 0.528-0.744. Notably, models using predicted features consistently outperform those using oracle features derived from the true future signals--the theoretical upper bound--suggesting effective noise filtering through learned sequence representations. Chronos models quickly reach performance saturation regardless of training depth, highlighting challenges in tokenizing continuous physiological time series. The proposed approach advances implicit feature engineering for wearable stress monitoring by leveraging forecasting as a powerful inductive bias, thereby improving robustness and providing insights into the limitations of the foundation model for physiological signals.

7
Reward-Based Equilibrium Propagation

Kubo, Y.

2026-08-05 neuroscience 10.64898/2026.07.30.741817 medRxiv
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Equilibrium propagation (EP) is a biologically plausible alternative to backpropagation for training neural networks. EP typically relies on free and nudged dynamical phases: during the free phase, the network relaxes toward an equilibrium state, whereas during nudging, the output state is perturbed toward a target using a teaching signal. However, it remains unclear whether the brain has access to such explicit target signals. Inspired by Attention-Gated Brain Propagation (BrainProp), a reward-based learning framework proposed by Pozzi et al. (2020), we introduce a reward-based variant of EP that replaces full target-based nudging with a selected-output binary reward signal. The proposed method updates the network using only the chosen class and whether that choice is correct, without directly revealing the full target vector. We evaluate the method on MNIST, Fashion-MNIST, and CIFAR-10 using both multilayer perceptrons and convolutional neural networks. The proposed reward-based EP achieves performance close to that of conventional EP across all three datasets, although it generally converges more slowly during the early stages of training. Generalization-gap analyses show similar behavior for the two methods on MNIST and Fashion-MNIST, while reward-based EP exhibits a smaller training-test accuracy gap during later training on CIFAR-10. We further investigate the effect of the exploration probability used during stochastic class selection and find that moderate exploration can provide small performance improvements, although its effect is dataset-dependent. These results demonstrate that EP can learn effectively from sparse, action-specific reward feedback rather than a complete supervised target.

8
Benchmarking Clustering Strategies for High-Dimensional Spike Time-Windows Data from Multi-Electrode Arrays

Sacchi, L.; Sommariva, S.; Unkel, M. A.; De Vrij, F. M.; Campi, C.

2026-09-23 neuroscience 10.64898/2026.09.17.752158 medRxiv
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From a statistical point of view, clustering spike time-windows from multi-electrode arrays (MEAs) recordings is a challenging high-dimensional, unsupervised clustering task where stationarity, commonly assumed in standard time-series analysis, is often violated and for which a gold standard is currently unavailable. Here we aim at providing practical guidance on how to cluster this type of data by systematically comparing 108 clustering pipelines differing along three main dimensions: (i) the data feature space; (ii) the metrics used to quantify distance between data points; and (iii) the clustering algorithm. For our benchmark we used both labeled synthetic data, mimicking four physiologically-inspired classes of spike time-windows, and a set of real MEAs recordings from a two-dimensional in-vitro neural culture. The performance of the competing pipelines was evaluated in terms of balanced accuracy and computational time when analyzing the synthetic datasets, while the Silhouette score was used for the real dataset, where no ground-truth is available. Overall, our analysis shows that the best combination is formed by k-means with Euclidean distance applied after Principal Component Analysis (PCA) of the spike time-windows. Conversely, hierarchical clustering showed the highest computational burden, while Independent Component Analysis and kernel PCA provided less effective noise suppression.

9
Concurrent model evidence computation and posterior sampling in continuous attractor network subspaces

Ren, Y.; Chen, Z.; Deans, H.; Wu, Y.; Zhang, W.

2026-09-08 neuroscience 10.64898/2026.09.02.748767 medRxiv
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Extensive studies suggest the brain performs Bayesian inference to infer the latent world states. It is a fundamental neuroscience question that how canonical recurrent neural circuits in the brain implement Bayesian inference. Many existing theoretical studies focused on how the recurrent circuits compute the posterior, while largely overlooking how the circuits compute the model evidence (normalization constant in Bayes' theorem), a key quantity that measures how well a model explains the observed data.Thus, it remains largely unknown about how the recurrent circuits compute the model evidence. The present study performs rigorous theoretical analyses of the continuous attractor networks, a canonical recurrent circuit model, and reveals that the nonlinear circuit dynamics can simultaneously compute the posterior and model evidence in first two dominant subspaces within the circuit dynamics. Specifically, the circuit dynamics in the stimulus feature subspace implements the Langevin posterior sampling, and the circuit dynamics in the subspace of total neuronal activity computes the model evidence in a way analogous to the evidence lower bound in stochastic variational inference. We further extend the circuit model to compute the model evidence of multiple inputs, and simulations validate the computation in the network. Our work for the first time reveals the concurrent model evidence and posterior sampling in subspaces in continuous attractor networks, significantly deepen our understanding of the computational algorithms adopted by the neural circuits.

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Conditional Spatial Classification of Expert-Confirmed Interictal Epileptiform Discharge Epochs: An EEG-ECG Ablation and SHAP Analysis

Plabon, A. M.; Mukit, A.; Neyamul, M.; Jehady, O. F.; Zuba, F. T.; Mina, M. F.; Islam, T.

2026-08-19 bioengineering 10.64898/2026.08.13.744348 medRxiv
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Interictal epileptiform discharges (IEDs) are diagnostically important EEG abnormalities observed between seizures. This study addresses a conditional spatial-classification task where every analyzed four-second epoch had already been reviewed and confirmed by experts as containing an IED, and the model assigned that epoch to one of five predefined scalp-distribution categories (generalized, frontal, temporal, occipital, or centro-parietal). The analysis therefore does not evaluate IED-versus-non-IED detection. After preprocessing, 2,514 IED-labelled epochs were analyzed using identical stratified epoch-level partitions, SMOTE based training, 26 handcrafted features per included channel, and multiple machine-learning classifiers. A staged channel ablation compared 19-channel scalp EEG, 21-channel EEG with ECG, and the complete 29-channel input containing scalp EEG, referential, ECG, and EMG channels. The best EEG-only result was obtained with linear discriminant analysis (88.89% test accuracy). CatBoost achieved 93.25% on EEG with ECG channel and 94.44% with the whole channel set. All eight directly comparable classifiers showed numerically higher test accuracy after ECG channel was added; for CatBoost, the increase was 6.35 percentage points. In the EEG with ECG channel, CatBoost model on ECG channel on right and left arm received respectively 15.79% and 15.12% of normalized global SHAP attribution, and beta-band power was the leading of all features (18.76%). These SHAP values indicate model-specific predictive contributions and do not establish physiological biomarkers, causal autonomic mechanisms, or clinical localization. The findings support a limited methodological conclusion which is ECG-derived features were associated with improved internal epoch-level categorization of expert-confirmed IED epochs. They do not establish IED detection, artifact rejection, independent EMG effects, or generalization to unseen patients.

11
Action Potential Thresholds and Excitability from the Geometry of Membrane Potential

Herrera-Valdez, M. A.

2026-08-26 neuroscience 10.64898/2026.08.21.746364 medRxiv
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A novel mathematical framework to define the threshold of action potentials in excitable cells is presented. Unlike previously applied methods that rely on approximations or bifurcations, the approach focuses on the geometry of membrane potential trajectories. The changes in concavity during the upstroke of an action potential can be directly obtained from a time series of voltages. The concavity criterion is then extended to models based on autonomous dynamical systems where the changes in concavity can be obtained analytically from a curve of inflection points in phase space. The inflection point manifold defines a region required for excitability: all the orbits that cross it contain action potentials, and all the trajectories that contain action potentials are in it. This analytical principle can then be used to define excitability in a dynamical system, and also a measure of excitability that enables quantification and comparisons of excitability across dynamical system. The measure provides a way to compare the excitabilities of systems that model neurons with different electrophysiological phenotypes and consider different stimulus conditions. The traditionally vague physiological concept of electrical excitability is transformed into a rigorous analytical description by considering the time-dependent curvature of the membrane potential. The criterion is robust across smooth, single compartment models of electrical excitability and can be can be extended to single compartment models in higher dimensions, and multicompartment models as well.

12
Improving the Hodgkin-Huxley Models of Ionic Conductance and Action Potential Generation

Djioua, M.

2026-08-10 neuroscience 10.64898/2026.08.04.742717 medRxiv
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This study presents improvements to the Hodgkin-Huxley (HH) models of ionic conductance and action potential generation. Sodium and potassium conductances are expressed by a single analytical formula describing the impulse response of a convolution of exponential distributions within a short-memory integration space. Treating transmembrane ion transit duration as a random variable, conductance profiles are interpreted as realizations of the probability density functions governing ionic movements. Applying the central limit theorem, the lognormal distribution emerges as the asymptotic profile of ionic conductances, constituting a fundamental primitive for such biosignals. A temporal state-transition paradigm describes the action potential waveform through four successive membrane potential transitions. Applied to electrophysiological recordings from lamprey reticulospinal neurons, this framework enables indirect estimation of key physiological quantities, including depolarization threshold, Nernst potentials, and net ion fluxes across the membrane. These advances open new perspectives for parameter estimation from experimental data and neuronal network simulation.

13
Full stack academic publishing in seizures with artificial intelligence: a cautionary tale

Kerr, W. T.; Pellinen, J.; McFarlane, K. N.; Goldenholz, D. M.

2026-10-11 neurology 10.64898/2026.10.07.26363237 medRxiv
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Significance: There is potential for generative artificial intelligence (AI) to perform "full stack" academic publishing, including comprehensive manuscript fabrication, "peer"-review, and editorial decision making. This study evaluated the benefits and cautions in using AI for full stack academic publishing in clinical research about seizures. Methods: Three epileptologists each selected 1 published manuscript in Epilepsia and produced an AI-fabricated manuscript about seizures. AI tools were then used to perform "peer"-review and make editorial decisions with minimal human supervision. The rates of identifying AI-fabricated manuscripts and editorial decisions among the epileptologists was analyzed, and epileptologists' observations on how AI differed from typical human "peer"-review and editorial decisions was collected. Results: Four of 6 (67%) pairs of AI-fabricated and human-generated manuscripts were correctly identified. Only 1 AI-fabricated manuscript was editorially rejected, whereas another had a subtle indicator of fabrication. When compared to human content, AI generated content was comprehensive, detailed, and based on the highest standard of academic publication. However, generated content was more verbose, used more structured responses, and more critical feedback. Conclusions: These results demonstrate that the quality of AI-fabricated manuscripts about clinical research in seizures was sufficiently high that the current methods of peer and editorial review could not easily distinguish fabricated content compared to human-written content. Moreover, AI review and editorial decisions were high quality and appeared reasonable in many cases. AI tools have matured to the point that there should be thoughtful policies that permit AI assistance but prohibit insufficiently supervised autonomous scientific submissions, reviews, and editorial decisions.

14
Computational simulation reveals the critical role of spike-timing-dependent plasticity in synchrony

Huang, Y.; Lankarany, M.; D'Eleuterio, G.

2026-09-22 neuroscience 10.64898/2026.08.27.747601 medRxiv
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Emerging research on desynchronization reveals strong relations to memory formation and recollection with much of the evidence originating from studies of the hippocampus, a brain region central to memory processing. However, growing evidence emphasizing the role of desynchronization is accompanied by challenges, most notably the synchronization/desynchronization conundrum. The conundrum arises from an apparent contradiction between learning and Shannon's information theory: spike-timing-dependent plasticity (STDP) acquires information via synchronized populational activity whereas information theory suggests that information channel is encoded through higher variability. Both frameworks are well-founded. Learning is widely accepted as the mathematical abstraction of STDP while Shannon's information theory showcases its power ubiquitously across fields from communication systems to neuroscience. Here, we propose that learning and Shannon's information theory are not necessarily opposing principles. Rather, learning plays a critical role in the process of synchronization and desynchronization. To justify our claim, we conduct computational simulations based on a Hodgkin-Huxley neuronal model coupled with NMDA, AMPA, and GABA synapses with inputs of biologically realistic spiking data. Our results show that enabling STDP significantly influences synchronization and desynchronization dynamics. Specifically, we find that STDP and desynchronization form a regulatory loop, in which STDP regulates the level of synchrony, and synchrony regulates subsequent learning strength. Further study reveals STDP is capable of switching neurons from synchronization to desynchronization. This framework mitigates the synchronization/desynchronization conundrum by clarifying the relationship between desynchronization and learning, and offers a new perspective on how synchrony contributes to memory formation and recollection.

15
Quantifying User Engagement with the Helpilepsy Seizure Diary

Davies, J.; Biondi, A.; Viana, P. F.; Ampe, L.; Schreiber, J.; Richardson, M. P.

2026-08-07 health informatics 10.64898/2026.08.05.26359796 medRxiv
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Seizure diaries are one of the most useful sources of information in the management of epilepsy, however patient engagement with them can be sporadic. Sustained participation with seizure diaries affects the completeness and reliability of self-reported data, so it is vital to be able to measure engagement. To facilitate this, we create a multidimensional engagement metric with which to characterize how patients interact with their seizure diary. We utilise data from the Helpilepsy, a seizure diary application, common features found in application engagement metrics in business settings, and well understood clinical features to do this. Clustering is then performed to isolate different user groups based on how engaged they are, and these groups are studied to understand what drives the differences in engagement. We found three groups emerge from the clustering: low, medium and highly engaged users. Investigating these groups further, we put together a ``profile" for highly-engaged users. We find that they tend to be older at the point of diagnosis, and have had epilepsy for longer than the other users. We also find they tend to have had more medications, have higher doses of common anti-seizure medications, and they have more medications typically given to those with refractory epilepsy. The implications for e-diary design are that more attention should be given to those newer to epilepsy in the onboarding phase. Also, engagement is not necessarily based on just the upload of seizures, with other features of an e-diary being important to be filled in.

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CLEAR-FORCE: A reservoir computing framework for closed-loop brain stimulation

Moreno-Gris, A.; Godin, C.; Thivierge, J.-P.

2026-10-12 neuroscience 10.64898/2026.10.05.756709 medRxiv
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Electrical stimulation of brain activity has emerged as a key therapeutic intervention for neurological diseases. The success of these approaches relies on precisely tuned stimulation parameters. A major challenge is that these parameters should ideally be adjusted in real-time based on changes in brain activity. Closed-loop controllers address this challenge by monitoring brain activity and adapting stimulation according to ongoing changes in neural dynamics. While machine learning has been helpful in this context, closed-loop controllers typically do not adapt in real-time to fluctuations in brain activity. Here, we propose a novel framework based on reservoir computing to train a closed-loop, real-time neural controller. This approach, termed CLEAR-FORCE, trains the output weights of a recurrent network based on a combination of target signals and feedback from brain activity. Two series of simulations were performed, where the controller was successful at (1) inducing neural oscillations in a population of spiking neurons and (2) suppressing pathological oscillations. This framework provides a promising avenue for the implementation of neural controllers in low-powered, real-time, and adaptive hardware that harnesses machine learning for the personalized treatment of brain disorders.

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Countering Neural Activity Drift: Sustained Long-term Seizure Prediction Using an Evolutionary Machine-Learning Framework on Continuous Intracranial EEG

Montoya-Galvez, J.; Ivankovic, K.; Nazari, M.; Principe, A.; Rocamora, R.

2026-09-14 neurology 10.64898/2026.09.14.26359203 medRxiv
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Objective: Seizure prediction in drug-resistant epilepsy remains a major biomedical challenge. Traditional machine learning approaches rely heavily on segmented offline testing, which suffers from artificial class rebalancing, hides neural activity drift over time, and severely inflates performance estimates. This study introduces an online evolutionary framework designed for realistic brain-computer interface validation and addresses performance degradation caused by neural drift. Methods: We present the first publicly available, continuous long-term stereoelectroencephalography dataset for seizure prediction, tracking 16 patients across 664.9 hours of data and 121 seizures. An offline combinatorial analysis evaluated pipeline decisions (referencing, frequency bands, functional connectivity metrics, and classifiers). The highest-performing offline elements, namely monopolar referencing, cross-correlation-based connectivity matrices, and Random Forests classifiers, were evaluated under realistic class imbalances in a pseudo-prospective online framework. Candidate models (N = 1,000 per patient) were evolved across continuous streams, while a data-driven approach targeted patient-specific epileptogenic networks for input channel reduction. Results: Transitioning from offline to online evaluation demonstrated a prominent performance drop, with mean AUROC degrading from 90% to 57.9%, confirming offline metrics conceal temporal neural drift. However, our online evolutionary framework identified models achieving complete event-level seizure prediction in 75% of patients (and all but one seizure in 87.5%). Restricting inputs to the estimated epileptogenic network identified using our previously proposed approach reduced implanted contact requirements by 79.12% while providing superior predictive performance over clinically resected areas. Significance: This work demonstrates that actionable, deterministic seizure prediction is achievable when paired with modern computational capability. Because 1,000 candidate models represent a conservative proof-of-concept search budget, scaling search spaces in production environments can further expand optimal interictal sampling and prediction yields. By providing both a continuous benchmark dataset and a standardized online evaluation protocol, this framework offers a foundation for self-adapting closed-loop devices capable of post-event retraining and long-term deployment in clinical neuromodulatory.

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BRIDGE: A Computational Workflow from Single Neurons to Network of Mean-Field Models

Carannante, I.; Depannemaecker, D.; Woodman, M.; Purohit, P.; Destexhe, A.

2026-08-06 neuroscience 10.64898/2026.07.31.742067 medRxiv
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Mean-field models are extensively used in large-scale brain simulations because they provide a wieldy description of population dynamics while preserving key features of neural activity. Despite their widespread adoption, no common and reproducible methodology currently exists to systematically derive and validate mean-field models starting from biologically grounded single neuron dynamics. As a result, implementations are often ad hoc, difficult to reproduce and rarely reusable. Here we introduce BRIDGE, a modular, open-source Python pipeline that enables the bottom-up reconstruction, analysis, validation, and simulation of mean-field models from single neurons. The framework integrates single neurons modelling, network simulations, extraction of population statistics, parameters analysis, quantitative comparisons between spiking neural networks and corresponding mean-field representations, and simulation of network of mean-fields. Its flexible architecture allows users to incorporate different neuron models and to generate region-specific or state-dependent mean-field formulations. BRIDGE provides a reproducible foundation for developing biologically informed mean-field models suitable for large-scale and whole-brain simulations, supporting the transition from generic homogeneous population models toward region-specific ones. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/742067v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1124404org.highwire.dtl.DTLVardef@2f8b2aorg.highwire.dtl.DTLVardef@1598f37org.highwire.dtl.DTLVardef@c9814b_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Bayesian heart-rate entropy identifies autonomic dynamics during seizure evolution: a reproducible pilot study

Olaciregui-Dague, K. R.; Rosas, F. E.; Gutierrez-Gomez, A.; Surges, R.; Mormann, F. E.; Kringelbach, M. L.

2026-08-04 neuroscience 10.64898/2026.07.30.741763 medRxiv
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Epileptic seizures are accompanied by profound alterations in autonomic regulation, yet the physiological information encoded in cardiac dynamics remains incompletely understood. Bayesian heart-rate (HR) entropy has recently been proposed as a probabilistic measure of cardiac dynamics, but whether it captures clinically meaningful aspects of seizure physiology--such as behavioral awareness or seizure evolution--has not been established. We estimated Bayesian HR entropy from electrocardiographic recordings acquired during video-electroencephalographic monitoring using the BayesianAtHeart framework. Entropy-derived measures were integrated with quality-controlled clinical metadata to generate a frozen seizure-level analysis dataset, from which all subsequent analyses were performed. Associations between seizure-average Bayesian HR entropy and clinical variables were evaluated using linear mixed-effects models accounting for repeated seizures within patients, and time-resolved entropy trajectories were analyzed descriptively. Following ECG quality control, Bayesian HR entropy was successfully estimated for 51 of 67 seizures from 10 patients; the remaining 16 seizures were excluded because ECG quality was insufficient. Forty-eight seizures with complete awareness classification comprised the primary analysis cohort. Bayesian HR entropy was not associated with ictal awareness across seizure-average analyses, mixed-effects models, or time-resolved entropy trajectories. Instead, seizure duration emerged as the strongest clinical correlate of Bayesian HR entropy, with longer seizures exhibiting progressively lower Bayesian HR entropy. Time-resolved analyses indicated that this association reflected a gradual decline in entropy during seizure evolution rather than lower Bayesian HR entropy at seizure onset. Post hoc sensitivity analyses showed that this association was not attributable to selection bias or to the number of beat-to-beat intervals available to the entropy estimator, and that duration, rather than stable between-patient differences, was the dominant source of entropy variance. Entropy was not generally reduced during seizures relative to a pre-ictal baseline; instead, the variability of the entropy trajectory declined progressively with seizure duration, more strongly than its mean. These findings suggest that Bayesian HR entropy primarily reflects the evolving organization of autonomic regulation during seizures rather than behavioral awareness. Beyond identifying seizure duration as the strongest correlate of Bayesian HR entropy in this cohort, this study establishes a fully reproducible computational framework for Bayesian HR entropy analysis that provides a foundation for future prospective investigations of autonomic dynamics in epilepsy.

20
The effects of temporal smoothing and interpolation on EEG microstate parameters, syntax, and our view of resting-state brain dynamics

von Wegner, F.; Hermann, G.; Toedt, I.; Todtenhaupt, I. K.; Laufs, H.

2026-10-08 neuroscience 10.64898/2026.09.30.755764 medRxiv
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Microstate analysis studies dynamic brain activity through a discrete representation of electroencephalographic (EEG) signals and their topography. While the body of literature describing findings in diverse experimental and clinical settings is growing rapidly, the effects of several core components of the microstate algorithm are still insufficiently understood. This study systematically investigates how two common temporal smoothing algorithms, parametric smoothing and GFP peak interpolation, influence a wide range of microstate sequence parameters, and how they shape the integrated picture of brain dynamics inferred from these metrics. We study eyes-closed resting-state EEG recordings from N=201 healthy subjects from a public EEG database. For the elementary temporal metrics, we find that widening smoothing windows markedly increase microstate duration, reduce occurrence rates, but leave coverage mostly unaffected. In terms of simple syntax properties, smoothing windows above 30 ms yield an inconsistent picture with a memoryless, first-order Markov structure at short time scales, but a positive Hurst phenomenon suggestive of long-range correlations at long time scales. Evidence of asymmetry and non-equilibrium dynamics are suppressed by smoothing. At intermediate time scales, microstate periodicity was only observed up to a window size of 28 ms. Smoothing had a strong impact on the complexity metrics entropy rate and excess entropy, decreasing the former and increasing the latter. For most metrics, the effects of GFP peak interpolation were comparable to those of smoothing windows in the range between 28 ms and 44 ms. In conclusion, elementary and higher-order microstate parameters must be interpreted in the context of preprocessing, as many parameters change continuously with smoothing intensity. This limits the comparability of microstate parameters obtained with different preprocessing settings. Strong smoothing with a window size above 30 ms or GFP peak interpolation yields a fundamentally different picture of resting state brain dynamics, i.e. that of a memoryless, aperiodic, time-reversible first-order Markov chain. Since insights from other neurophysiological modalities suggest that time series memory and time-irreversibility are markers of normal brain activity, our recommendation is to avoid intense smoothing to minimize alterations of the initial sequences.